Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

DNMT3A (Q9Y6K1) - Overview - Molecular Target Synopsis

Protein


DNMT3A, DNA (cytosine-5)-methyltransferase 3A
Enzyme Classification 2.1.1.37
UniProt Q9Y6K1

Also Known as DNM3A_HUMAN, DNMT3A

Required for genome-wide de novo methylation and is essential for the establishment of DNA methylation patterns during development. DNA methylation is coordinated with methylation of histones. It modifies DNA in a non-processive manner and also methylates non-CpG sites. May preferentially methylate DNA linker between 2 nucleosomal cores and is inhibited by histone H1. Plays a role in paternal and maternal imprinting. Required for methylation of most imprinted loci in germ cells. Acts as a transcriptional corepressor for ZBTB18. Recruited to trimethylated 'Lys-36' of histone H3 (H3K36me3) sites. Can actively repress transcription through the recruitment of HDAC activity. Heterotetramer composed of 1 DNMT3A homodimer and 2 DNMT3L subunits (DNMT3L-DNMT3A-DNMT3A-DNMT3L). Interacts with UBC9, PIAS1 and PIAS2 (By similarity). Binds the ZBTB18 transcriptional repressor. Interacts with SETDB1. Associates with HDAC1 through its ADD domain. Interacts with UHRF1 (By similarity). Interacts with DNMT1 and DNMT3B. Interacts with the PRC2/EED-EZH2 complex. Interacts with MPHOSPH8. Interacts with histone H3 that is not methylated at 'Lys-4' (H3K4).

6F57
CRYSTAL STRUCTURE OF DNMT3A-DNMT3L IN COMPLEX WITH SINGLE CPG- CONTAINING DNA
RCSB/PDB
Inspect Structure
See all 3D Structures for DNMT3A

Isoforms / Transcripts (Protein Coding)


Drugs


DNMT3A is targeted by Approved Drugs Azacitidine, Decitabine. (see details)
Azacitidine
Decitabine

Sub-cellular localization


UniProt: DNMT3A is active in the following subcellular-locations: cytoplasm, nucleus.
GO terms: DNMT3A is active in the following subcellular-locations: chromosome, cytoplasm, euchromatin, nuclear heterochromatin, nuclear matrix, nucleoplasm, nucleus, XY body.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project DNMT3A has gain in 2 cell-lines, loss in 0 cell-lines and no signal in 1003 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: CCRF_CEM, MOLT_4, OVCAR_3

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: DMS 79, SK-N-FI, NCI-H187

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: SK-N-SH, SK-N-SH_RA, NHLF

(see details)

3D Structures


For DNMT3A there are:
13 structures (26 chains) solved
8 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


DNMT3A has been screened with 75 compounds (125 bioactivities), 1 compounds have bioactivities that show binding affinity of <= 500nM (1 bioactivities). (see details)